Brain-Tissue Loss Could Be Positive Development

It seems that few things worse could befall a child than to start hearing threatening voices, thinking bizarre thoughts, and losing brain tissue in increasing amounts as time goes by.

While that may be the fate of youngsters who develop schizophrenia, one study suggests that the situation isn’t completely bleak. Alexandra Sporn, M.D., of the Child Psychiatry Branch of the National Institute of Mental Health, and colleagues found that brain tissue loss seems to plateau once youngsters with schizophrenia approach adulthood. Even more intriguingly, the speed of brain tissue loss seems to be coupled with clinical improvement.

The findings were reported in the December 2003 American Journal of Psychiatry.

The researchers used magnetic resonance imaging to scan the brains of 39 adolescents with schizophrenia, both at baseline, that is, when they were around 14 or 15 years of age, and then during one or more follow-up periods, which were spaced approximately two years apart. Eighteen of the 39 subjects received two scans, 14 received three scans, three received four scans, and four received five scans. Each time the youngsters were scanned, they were also assessed clinically and neuropsychologically. Sporn and her colleagues also selected as control subjects 43 age- and gender-matched youngsters from a larger pool of psychologically healthy subjects participating in a study of normal brain development at NIMH. MRI scans were performed on the brains of these control subjects around the same times as they were performed on the subjects with schizophrenia.

Sporn and her group then compared the brain scans of the youth with schizophrenia with those of the control youth. Some of the results, on the face of it, did not appear encouraging.

Both groups lost gray matter over time, and both groups lost gray matter in a back-to-front cortical wave, but the loss was significantly greater (around 19 percent greater) in the schizophrenia youngsters. What’s more, the loss appeared to be due to schizophrenia, since the investigators could find no significant association between the rate of gray-matter reduction and the types or doses of medications the schizophrenia subjects were receiving.

Other results, however, appeared more propitious. In most schizophrenia subjects, the rate of gray-matter attrition appeared to slow down as they approached adulthood. True, “this observation of a leveling off of gray-matter reduction is still preliminary,” the researchers cautioned in their study report, “and requires further validation with larger numbers of subjects and a longer follow-up period.”

Also, contrary to what the investigators expected, a significant link was found in the schizophrenia subjects between the rate of gray-matter loss and clinical improvement. “Although measures of improvement can be confounded with baseline symptom severity,” the scientists acknowledged, “the strong correlation of brain volume loss with percent improvement in symptom measures argues against this interpretation.”

Yet how could accelerated brain-tissue loss help schizophrenia youth think and function better? Very simply, Sporn and her team proposed in their report: “An association of greater clinical improvement with a faster rate of gray-matter decline, if replicated, might be viewed as, in part, a compensatory ‘pruning’ of malfunctioning neural circuits, which is consistent with some neurodevelopmental models of schizophrenia.”

The study, “Progressive Brain Volume Loss During Adolescence in Childhood-Onset Schizophrenia,” is posted online at http://ajp.psychiatryonline.org/cgi/content/full/160/12/2181?. ▪

Am J Psychiatry 2003 160 2181